Abstract
Contact hypersensitivity (CHS) is a common T cell-mediated skin disease induced by epicutaneous sensitization to haptens. Mast cells (MCs) are widely deployed in the skin and can be activated during CHS responses to secrete diverse products, including some with pro-inflammatory and anti-inflammatory functions. Conflicting results have been obtained regarding pathogenic versus protective roles of MCs in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products in vivo. Notably, fluorescent avidin-based two-photon imaging approaches enable in vivo selective labeling and simultaneous tracking of MC secretory granules (e.g., during MC degranulation) and MC gene activation by real-time longitudinal intravital microscopy in living mice. The combination of such genetic and imaging tools has shed new light on the controversial role played by MCs in mouse models of CHS. On the one hand, they can amplify CHS responses of mild severity while, on the other hand, can limit the inflammation and tissue injury associated with more severe or chronic models, in part by representing an initial source of the anti-inflammatory cytokine IL-10.
Highlights
Allergic contact dermatitis (ACD), and its animal model contact hypersensitivity (CHS), are T cellmediated skin inflammatory diseases caused by delayed-type hypersensitivity responses to environmental allergens [1,2,3]
We have reviewed evidence that Mast cells (MCs) can either limit or contribute to the inflammation and tissue pathology of Contact hypersensitivity (CHS) depending on the severity of the model used
It is tempting to speculate that, depending on their activation threshold, MCs could either become pro-inflammatory, i.e., “type 1” or inflammatory MCs, or anti-inflammatory, i.e., “type 2” or immunoregulatory MCs, as previously reported for other immune cells, such as macrophages [49]. Whether these different functions of MCs can occur in settings other than CHS responses and the extent to which they reflect distinct MC phenotypes within the same population or different MC subpopulations expressing specific phenotypes and transcriptional programs remains to be investigated
Summary
Reveal Pro-Inflammatory and Immunoregulatory Roles of Mast Cells in Contact Hypersensitivity. Mast cells (MCs) are widely deployed in the skin and can be activated during CHS responses to secrete diverse products, including some with pro-inflammatory and anti-inflammatory functions. Fluorescent avidin-based two-photon imaging approaches enable in vivo selective labeling and simultaneous tracking of MC secretory granules (e.g., during MC degranulation) and MC gene activation by real-time longitudinal intravital microscopy in living mice. The combination of such genetic and imaging tools has shed new light on the controversial role played by MCs in mouse models of CHS.
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